Adrenal glands, hormones from

Water and electrolyte metabohsm is regulated by aldosterone from the adrenal gland, renin from the kidney, and vasopressin (antidiuretic hormone [ADH]) from the posterior pituitary gland (see Chapters 45 and 46). 

Kendall, Edward Calvin (1886-1972) U.S. biochemist who studied the hormones produced by the outer zone (cortex) of the adrenal gland and, from his findings, synthesized cortisone. This led to the valuable range of corticosteroid drugs. In 1950, Kendall and his colleague, Philip Hench, were awarded the Nobel Prize in physiology or medicine. 

It was known as early as 1927 that the adrenal glands of mammalian species secrete a series of substances essential to the survival of the individual. The hormonal nature of these secretions was suggested by the observation that extracts of the adrenal gland and more specifically of the outer portion of that organ (cortex) would ensure survival of animals whose adrenals had been excised. By 1943 no fewer than 28 steroids had been isolated from adrenal cortical extracts. These compounds were found to be involved in the regulation of such diverse and basic processes as electrolyte balance, carbohydrate metabolism, and resistance to trauma, to name only a few. 

Adrenaline (epinephrine) is a catecholamine, which is released as a neurotransmitter from neurons in the central nervous system and as a hormone from chromaffin cells of the adrenal gland. Adrenaline is required for increased metabolic and cardiovascular demand during stress. Its cellular actions are mediated via plasma membrane bound G-protein-coupled receptors. 

The adrenergic system is an essential regulator that increases cardiovascular and metabolic capacity during situations ofstress, exercise, and disease. Nerve cells in the central and peripheral nervous system synthesize and secrete the neurotransmitters noradrenaline and adrenaline. In the peripheral nervous system, noradrenaline and adrenaline are released from two different sites noradrenaline is the principal neurotransmitter of sympathetic neurons that innervate many organs and tissues. In contrast, adrenaline, and to a lesser degree noradrenaline, is produced and secreted from the adrenal gland into the circulation (Fig. 1). Thus, the actions of noradrenaline are mostly restricted to the sites of release from sympathetic nerves, whereas adrenaline acts as a hormone to stimulate many different cells via the blood stream. 

Corticosteroids are hormones secreted from the adrenal cortex. These hormones arise from the cortex of the adrenal gland and are made from the crystalline steroid alcohol cholesterol. Synthetic forms of the natural adrenal cortical hormones are available The potent antiinflammatory action of the corticosteroids makes these drugs useful in the treatment of many types of musculoskeletal disorders. The corticosteroids are discussed in Chapter 50. 

Because ACTH stimulates the release of glucocorticoids from the adrenal gland, adverse reactions seen with the administration of this hormone are similar to those seen with the glucocorticoids (see Display 50-2) and affect many body systems. The most common adverse reactions include ... 

Adrenocorticotropic hormone A hormone secreted by the anterior pituitary that controls secretion of cortisol from the adrenal glands also referred to as corticotropin. 

A somewhat related sequence leads to trilostane (111), a compound that inhibits the adrenal gland more specifically the agent blocks some of the metabolic responses elicited by the adrenal hormone ACTH in experimental animals. Reaction of the hydroxy-methylene derivative 108, obtained from testosterone, with hydroxylamine gives the corresponding isoxazole (109). Oxidation of the C-4,5 double bond by means... 

A nontrophic hormone acts on nonendocrine target tissues. For example, parathormone released from the parathyroid glands acts on bone tissue to stimulate the release of calcium into the blood. Aldosterone released from the cortical region of the adrenal glands acts on the kidney to stimulate the reabsorption of sodium into the blood. 

Adrenal medulla. Derived from neural crest tissue, the adrenal medulla forms the inner portion of the adrenal gland. It is the site of production of the catecholamines, epinephrine and norepinephrine, which serve as a circulating counterpart to the sympathetic neurotransmitter, norepinephrine, released directly from sympathetic neurons to the tissues. As such, the adrenal medulla and its hormonal products play an important role in the activity of the sympathetic nervous system. This is fully discussed in Chapter 9, which deals with the autonomic nervous system. 

The acute CNS effects of MDMA administration are mediated by the release of monoamine transmitters, with the subsequent activation of presynaptic and postsynaptic receptor sites.40 As specific examples in rats, MDMA suppresses 5-HT cell firing, evokes neuroendocrine secretion, and stimulates locomotor activity. MDMA-induced suppression of 5-HT cell firing in the dorsal and median raphe involves activation of presynaptic 5-HT1A autoreceptors by endogenous 5-HT.4142 Neuroendocrine effects of MDMA include secretion of prolactin from the anterior pituitary and corticosterone from the adrenal glands 43 Evidence supports the notion that these MDMA-induced hormonal effects are mediated via postsynaptic 5-HT2 receptors in the hypothalamus, which are activated by released 5-HT. MDMA elicits a unique profile of locomotor effects characterized by forward locomotion and elements of the 5-HT behavioral syndrome such as flattened body posture, Straub tail, and forepaw treading.44 6 The complex motor effects of MDMA are dependent on monoamine release followed by activation of multiple postsynaptic 5-HT and DA receptor subtypes in the brain,47 but the precise role of specific receptor subtypes is still under investigation. 

The catecholamines dopamine, norepinephrine and epinephrine are neurotransmitters and/or hormones in the periphery and in the CNS. Norepinephrine is a neurotransmitter in the brain as well as in postganglionic, sympathetic neurons. Dopamine, the precursor of norepinephrine, has biological activity in the periphery, most particularly in the kidney, and serves as a neurotransmitter in several important pathways in the CNS. Epinephrine, formed by the N-methylation of norepinephrine, is a hormone released from the adrenal gland, and it stimulates catecholamine receptors in a variety of organs. Small amounts of epinephrine are also found in the CNS, particularly in the brainstem. 

Most hormones are produced naturally in the body (e.g. adrenaline (II) is formed in the adrenal glands). From there, the hormone enters the bloodstream and is consumed chemically (a physiologist would say metabolized ) at the relevant sites in the body - in fact, adrenaline accumulates and is then broken down chemically in the muscles and lungs. Adrenaline is generated in equal amounts in men and women,... 

Disulfoton exposure altered catecholamine levels in animals, and this hormonal imbalance may be associated with elevated acetylcholine levels (Brzezinski 1969, 1972, 1973 Brzezinski and Ludwicki 1973 Brzezinski and Rusiecki 1970 Wysocka-Paruszewska 1970, 1971). In these studies, acute dosing with disulfoton caused increases in urinary and plasma noradrenaline and adrenaline levels, accompanied by decreases of adrenaline in the adrenal glands, in rats. In addition, the major urinary metabolite of catecholamine metabolism, 4-hydroxy-3-methoxymandelic acid (HMMA), was recovered in the urine from rats given acute doses of disulfoton (Wysocka-Paruszewska 1970,... 

Note that these structures are related to that for the amino acid tyrosine, from which they are derived. The adrenal glands, small pieces of tissue that ride on top of the kidneys, secrete these hormones. When they activate adrenergic receptors on the surface of muscle cells, adenylate cyclase is activated, increased cAMP results, and the cascade of events in muscle cells is started (figure 17.1). 

Epinephrine is a hormone synthesized in the adrenal glands from tyrosine (see p. 352). Its release is subject to neuronal control. This emergency hormone mainly acts on the blood vessels, heart, and metabolism. It constricts the blood vessels and thereby increases blood pressure (via ai and a2 receptors) it increases cardiac function (via P2 receptors) it promotes the degradation of glycogen into glucose in the liver and muscles (via P2 receptors) and it dilates the bronchia (also via P2 receptors). 

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